Drug-eluting stapes prosthesis

ABSTRACT

A medical implant device includes a prosthesis adapted to replace at least a portion of a bone. The prosthesis includes a drug-eluting polymer adapted to deliver a drug to at least a portion of an area surrounding the prosthesis.

CROSS-REFERENCE TO RELATED APPLICATION

This application claims priority to and the benefit of U.S. provisionalpatent Application No. 60/947,821, filed Jul. 3, 2007, the disclosure ofwhich is incorporated herein by reference in its entirety.

TECHNICAL FIELD

In various embodiments, the invention relates to devices and techniquesfor use in the surgical treatment of the middle ear. More particularly,described herein are embodiments of a drug-eluting stapes prosthesis,and associated methods of use, for relieving impaired conductive hearingof the middle ear and/or sensorineural hearing loss in the inner ear.

BACKGROUND

The human ear includes three parts, identified generally as the outerear, the middle ear and the inner ear. The middle ear includes threesmall bones. The malleus, or hammer, connects to the tympanic membrane,also known as the eardrum, of the outer ear. The malleus is in turnconnected to the incus, or anvil. The incus is connected to the stapes,or stirrup. These three small bones are also commonly referred to asossicles, or collectively as the ossicular chain. The three bonesoperate as a lever and piston system that amplifies the force of soundvibrations. The stapes is in turn connected to the oval window, orstapes footplate, of the inner ear. The stapes applies pressure at thestapes footplate, which is transmitted to parts of the cochlea of theinner ear.

Due to disease, trauma or congenital malformation, the ossicles of themiddle ear are sometimes damaged. One common cause is otosclerosis,which may result in fixation of the stapes. This may lessen or eliminatevibration of the stapes, resulting in a conductive hearing loss. As aresult of otosclerosis, and other conditions, approximately 30,000patients in the U.S. each year undergo a stapedectomy, which is asurgical procedure involving the removal of one of the bones of themiddle ear responsible for transmission of vibration from the eardrum tothe cochlea. Often, this procedure involves the replacement of thestapes bone with a prosthesis.

An exemplary technique for replacing the stapes bone with a prosthesisis shown in FIGS. 1A-1C, with a corresponding stapes prosthesis shown inFIG. 2. The stapes bone 110 is typically reconstructed by creating anopening 120 into the stapes footplate 130 by removal of a portion or allof the damaged stapes 110. The stapes prosthesis 200 is then placed intothe newly created opening 120. The prosthesis 200 is attached to aremaining middle ear ossicle 140, referred to as the anchoring ossicle,so that sound vibrations are transmitted from the ear drum to the stapesfootplate opening.

Designs for stapes prostheses vary somewhat, but in general, asillustrated in FIG. 2, they include a thin wire 210. The thin wire 210is fitted on one end of a piston element 220, often constructed from aplastic such as Teflon. The exposed end of the wire 210 is crimped tothe incus bone, and the piston end 220 is positioned within the hole 120created in the stapes footplate 130, within the inner ear. Theprosthesis 200 effectively mimics the function of the original stapes,carrying vibrations from the incus to the cochlea.

For approximately 6-10% of patients with a stapes prosthesis,otosclerosis is a continuing problem which may lead to failure of theprosthesis and the need for additional surgery. Drug compounds, such asbisphosphonates, help to prevent this continued bone resorption, buthave side effects that make site-specific delivery of the drug desirablecompared to systemic delivery.

The use of polymer-loaded matrices for delivery of drug to the middleear has been previously described. However, such devices are limited todrug delivery and, as such, a separate additional implanted device, suchas a stapes prosthesis, is still required to directly relieve theproblem causing the impaired hearing.

In addition, current drug delivery devices are often difficult to placewithin the middle ear, especially if the device is to be large enough tohold a useful amount of drug while also allowing delivery of a drugdirectly into the cochlea. This may limit the allowable room forplacement of an additional prosthetic device, or other treatment device,within the ear.

Other methods may also be utilized for delivery of a drug to the middleear. For example, direct injection of drugs may be possible, althoughthis may often be undesirable as it would require repeated invasivetreatments by a physician. Other devices, such as polymeric drugcarriers or microfluidic pumps, may also be implanted in a patient,allowing for the delivery of a drug to either the middle or inner ear.Again, however, a separate, additional, implanted device, such as astapes prosthesis, would still be required.

SUMMARY OF THE INVENTION

In various embodiments, the present invention relates to systems andmethods for providing a drug-eluting capability directly into a stapesprosthesis, or other medical implantable device. As a result, theexemplary systems, methods, and devices described herein enable drugdelivery directly to the middle and/or inner ear and, as such, may beused for treatment of problems such as, but not limited to, preventionof otosclerosis, treatment of tinnitus, prevention of cisplatin-basedototoxicity amongst cancer patients, and sensorineural hearing loss.This, in turn, allows for a single device to be used to directly relievea condition of the ear while also providing a method of delivering adrug.

One embodiment of the invention includes adding a drug-eluting functionto an existing implantable device, such as a stapes prosthesis. Thisresults in a device capable of providing both a drug delivery functionand a prosthetic function to a portion of a body, such as the middleand/or inner ear.

In one aspect, a medical implant device includes a prosthesis adapted toreplace at least a portion of a bone. The prosthesis includes adrug-eluting polymer adapted to deliver a drug to at least a portion ofan area surrounding the prosthesis.

The prosthesis may be a stapes prosthesis, which may include a wireportion and a piston portion. In one embodiment, the drug-elutingpolymer surrounds at least one section of the wire portion. In anotherembodiment, the piston portion includes the drug-eluting polymer. Thepiston portion may include a monolithic polymer matrix having drugmolecules distributed therethrough. The piston portion may include asolid exterior. The piston portion may also include a core, within thesolid exterior, that includes the drug-eluting polymer. In oneembodiment the piston portion includes a semi-permeable membrane, and/oran impermeable sheath.

In general, in another aspect, embodiments of the invention feature amethod of treating a portion of a body. The method includes removing adamaged portion of a body and inserting a prosthesis to replace thedamaged portion of the body. The prosthesis includes a drug-elutingpolymer adapted to deliver a drug to at least a portion of an areasurrounding the prosthesis.

In one embodiment, the damaged portion of the body includes a stapesbone. The prosthesis may therefore be a stapes prosthesis having, forexample, the structure described above.

In general, in another aspect, embodiments of the invention feature amethod for manufacturing a medical implant device. The method includescoupling a wire portion to a piston portion to form a prosthesis, atleast one of the wire portion and the piston portion including adrug-eluting polymer adapted to deliver a drug to at least a portion ofan area surrounding the prosthesis.

These and other objects, along with advantages and features of thepresent invention herein disclosed, will become more apparent throughreference to the following description, the accompanying drawings, andthe claims. Furthermore, it is to be understood that the features of thevarious embodiments described herein are not mutually exclusive and canexist in various combinations and permutations.

BRIEF DESCRIPTION OF THE DRAWINGS

In the drawings, like reference characters generally refer to the sameparts throughout the different views. Also, the drawings are notnecessarily to scale, emphasis instead generally being placed uponillustrating the principles of the invention. In the followingdescription, various embodiments of the present invention are describedwith reference to the following drawings, in which:

FIG. 1A is a schematic view of a typical middle ear prior to removal ofa stapes bone;

FIG. 1B is a schematic view of the middle ear of FIG. 1A, after removalof the stapes bone;

FIG. 1C is a schematic view of the middle ear of FIG. 1A, afterreplacement of the stapes bone with an exemplary stapes prosthesis;

FIG. 2 is a schematic side view of a standard stapes prosthesis;

FIG. 3 is a schematic side view of a stapes prosthesis, in accordancewith one embodiment of the invention;

FIG. 4 is a schematic side view of a stapes prosthesis with adrug-eluting polymer coating on the wire, in accordance with oneembodiment of the invention;

FIG. 5 is a schematic side view of a stapes prosthesis with a unitarydrug-eluting polymer piston section, in accordance with one embodimentof the invention;

FIG. 6 is a schematic side view of a stapes prosthesis with adrug-eluting core embedded within a polymer piston section, inaccordance with one embodiment of the invention; and

FIG. 7 is a schematic side view of a stapes prosthesis with adrug-eluting piston section embedded within an impermeable sheath, inaccordance with one embodiment of the invention.

DESCRIPTION

In general, embodiments of the present invention relate to systems andmethods for providing a stapes prosthesis, or other appropriate medicalprosthesis, with a drug-eluting function.

In one embodiment, the invention includes a drug-eluting stapesprosthesis in which a portion of the stapes prosthesis, such as a pistonor wire portion, is replaced with, covered with, or enhanced with apolymer formulation impregnated with a drug. This drug may then bereleased over time from the polymer formulation into the ear in acontrolled fashion.

FIG. 3 shows a stapes prosthesis 300 prior to coating a wire portion 310thereof with a drug-eluting material. The stapes prosthesis 300 includesa piston element 320 for positioning within and/or against a stapesfootplate, and the wire portion 310 for connection, for example, to theincus bone. The wire portion 310 includes a curved distal portion 330 toassist in connecting the wire portion 310 to the incus bone and crimpingthe wire portion 310 thereto. The piston element 320 and wire portion310 may each be of any appropriate size and shape to allow for itspositioning within an ear. For example, in one embodiment, the pistonelement 320 may range from 1 mm to 5 mm in length, and from 0.1 mm to 1mm in thickness, as appropriate. In alternative embodiments, the pistonelement 320 may be either larger or smaller, depending upon the geometryof the ear in which the stapes prosthesis 300 is to be placed.

In one embodiment, the wire portion 310 is constructed from a metal suchas titanium, nitinol, aluminum, stainless steel, or any otherappropriate metal or combinations thereof. In an alternative embodiment,the wire portion 310 is constructed from a plastic, a polymericmaterial, or any other appropriate material. The wire portion 310material may be selected to provide any appropriate material propertiesfor the stapes prosthesis 300, including, but not limited to, anydesired strength, flexibility, elastic and/or plastic deformability,chemical stability, sterility, and/or non-allergic property. The wireportion 310 may be attached to the piston portion 320 through anadhesive attachment, a threaded attachment, a pressure fitting, or anyother appropriate attachment.

In one embodiment, as illustrated in FIG. 4, a drug-eluting polymercoating 410 is coated onto the wire portion 310, or a section thereof,of the stapes prosthesis 300. The drug-eluting polymer coating 410 mayinclude, for example, drug particles dispersed within a polymer matrixsuch that the drug particles are released into the body at a rate andconcentration based, at least in part, on the specific properties of thedrug and the polymer matrix. The drug-eluting polymer coating 410 may bedegradable or non-degradable, as appropriate. The polymer matrix forholding and dispersing the drug particles may include materials such asplastics, metals, organic materials, biocompatible materials, compositematerials, or combinations thereof.

In an alternative embodiment, the drug-eluting polymer coating 410 maybe replaced with other materials and systems for releasing a drug intothe surrounding area. For example, in one embodiment, a drug may becoated directly onto the wire portion 310 as a solid, liquid, or gel.Upon placement within the ear, the drug may then dissolve, or otherwisebe released from the wire portion 310, and thereby be delivered to therequired location within the body. The drug may be coated to the wireportion 310 as a single layer of material, or be suspended within adegradable sterile material that dissolves within the body to releasethe drug. In an alternative embodiment, the wire portion 310 may be atleast partially hollow, with a drug stored within. The hollow wireportion 310 may be at least partially permeable, thereby allowing thedrug being stored within to be released into the surrounding area.

In other embodiments of the invention, the piston portion 320 isconfigured to provide drug-eluting properties in place of, or inaddition to, the drug-eluting wire portion 310. This drug-eluting pistonportion 320 may take a variety of forms. Exemplary embodiments aredescribed with reference to FIGS. 5-7.

In one embodiment, as illustrated in FIG. 5, a stapes prosthesis 500includes a wire portion 510 and a drug-eluting piston portion 520 thatincludes a single monolithic, non-degradable matrix, with drug moleculesevenly distributed throughout. The wire portion 510 may include any ofthe materials and properties described above. The piston portion 520 isconstructed from a drug-eluting polymer material including a polymermatrix configured to hold drug particles within and release the drugparticles into the surrounding area at a set rate when implanted withina body. The polymer matrix may include materials such as plastics,metals, organic materials, biocompatible materials, composite materials,or combinations thereof.

In alternative embodiments, the piston portion 520 includes a pluralityof sections, with one or more sections including the drug-elutingpolymer material and the other sections not be loaded with the drug. Thedifferent drug-eluting polymer sections may be configured to release thesame or different drugs at substantially similar or different rates, asappropriate.

In another embodiment, as illustrated in FIG. 6, a stapes prosthesis 600includes a wire portion 610 and a drug-eluting piston portion 620 thatincludes a solid exterior 640 with a core 630. The wire portion 610 mayinclude any of the materials and properties described above. The core630 includes a drug-eluting material configured to hold drug particleswithin and release the drug particles into the surrounding area at a setrate when implanted within a body. The core 630 may include any of thematerials for storing and releasing a drug described herein, such as,but not limited to, a polymer matrix, a gel, or a liquid. Examplematerials include, but are not limited to, degradable of non-degradablepolymer matrices, hydrogels, or liquids with drugs suspendedtherewithin. In an alternative embodiment, the core 630 may include ahollow section configured to provide storage for a drug.

The solid outer section 640 of the piston 620 is adapted to hold thecore 630 and limit the release of the drug or drugs to one or morespecific directions. The solid outer section 640 may be constructedfrom, for example, a metal, a plastic, a ceramic, and/or a polymericmaterial. In one embodiment, the outer section 640 is constructed fromthe same material as the polymer matrix core 630. In an alternativeembodiment, the outer section 640 and the polymer matrix core 630 areconstructed from different materials. In one embodiment, the drug isreleased through a semi-permeable membrane 660 positioned against thecore 630 and located at a distal end 650 of the piston portion 620. Thisconfiguration allows the drug to be released directly into the inner earthrough the opening in the stapes footplate, to which the piston portion620 is anchored, without being released into the middle ear. In analternative embodiment, no semi-permeable membrane 660 is employed.Rather, the core 630 is exposed directly to the surroundings, at thedistal end 650 of the piston portion 620.

The outer section 640 may alternatively or additionally include one ormore permeable sections on its outer side wall 670, thereby allowingdrug release into one or more specific areas around the outer side wall670 of the piston portion 620. As a result, the drug can be releasedinto the middle ear through the side wall 670 of the piston portion 620instead of, or in addition to, being released into the inner ear througha distal end 650 of the piston portion 620. These permeable sections mayinclude, but are not limited to, perforations and/or permeable orsemi-permeable membranes. In addition, a proximal end 680 of the pistonportion 620 may be configured to allow drug release.

In another embodiment of the invention, as illustrated in FIG. 7, adrug-eluting piston portion 720 of a stapes prosthesis 700 includes anon-permeable coating or impermeable sheath 730 (such as a metal film)that restricts drug release from the prosthesis 700 to a selected region770 of the piston portion 720.

In one embodiment, the impermeable sheath 730 provides an impermeablecovering for at least a portion of the drug eluting piston portion 720.The impermeable sheath 730 may be moveable and may be constructed fromany appropriate material including, but not limited to, a metal, aceramic, and/or a polymer. In operation, in one embodiment, theimpermeable sheath 730 is placed over a portion of the piston portion720 to restrict the release of a drug to one section of the side wall770 of the piston portion 720. In an alternative embodiment, the sheath730, rather than being impermeable, may include one or moreperforations, and/or permeable or semi-permeable sections, to allow adrug to be released therethrough. These perforations and/or permeablesections may be distributed over the sheath 730 in any appropriateconfiguration.

Other embodiments of the invention include a number of elements of theembodiments described above. For example, one embodiment of theinvention includes both a drug-eluting polymer covering the wire portionof the stapes prostheses in addition to a drug-eluting piston portion.In further embodiments of the invention, any combination of elementsdescribed herein may be used to allow the prosthesis to deliver a drug,or a number of separate drugs, to targeted portions of the middle and/orinner ear. These embodiments may include wire portions adapted todeliver one or more drugs, and piston portions adapted to deliver one ormore other drugs from a bottom portion of the prosthesis attached to thestapes footplate and/or out of the side and/or top of the piston.

In addition, other materials in addition to, or in place of, adrug-eluting polymer may be used in the construction of the prosthesis.These may include any appropriate biocompatible material, including, butnot limited to, a metal, a plastic, a composite material, orcombinations thereof.

The exemplary devices described herein feature a number of benefits overconventional stapes prostheses (such as the stapes prosthesis 200illustrated in FIG. 2), or other medical implants. For example,combining a drug delivery system with the prosthesis device reduces thenumber of separate components that must be inserted into the middle ear,thereby simplifying the stapedectomy procedure and increasing patientsafety. In one embodiment, the addition of the drug-eluting element tothe stapes prosthesis allows for the continued treatment of otosclerosisvia the drug-eluting prosthesis, without the need for any additionalimplants or procedures.

In addition, combining the drug-containing element with the prosthesisminimizes the diffusion distance the released drug must travel to reachthe desired site of action. Although, in general, a separate drugdelivery device implanted within the middle ear will be relatively closeto the desired site of action, due to the limited volume of the middleear, the closer the delivery device is placed to the desired site, thebetter. For example, for controlled release from small matrices, theobserved drug concentration drops off rapidly as you move away from thedevice, such that for some applications tissues located on the order ofa few millimeters from the device will not receive therapeuticallyuseful doses of drug.

Also, for embodiments in which the drug delivery system is placed withinthe piston of the stapes prosthesis, the distal end of the piston may beplaced in direct fluid communication with the inner ear, therebyenabling delivery of the drug directly to the inner ear, rather thanrelying on diffusion of the drug from the middle ear to the inner ear.This embodiment may be used, for example, in the treatment of cochlearotosclerosis, where delivery of one or more drugs directly into thecochlea, such as through the distal end of the prosthesis piston, may beof significant value. In one embodiment, drugs from the bisphosphonateclass are delivered, although, in other embodiments, other appropriatedrugs are delivered in place of, or in addition to, bisphosphonate classdrugs.

In one embodiment, combining the drug-eluting element into theprosthesis places a limit on the payload of drug that may be carried.For example, the piston may be on the order of 2-4 mm long and 0.6 mm indiameter, thus limiting the storage space for any drug to no more thanthat volume. However, even given these size constraints, appropriatedosages of drug may still be encapsulated in the device to providelong-term delivery of the drug.

In one specific example, a bisphosphonate drug, such as, but not limitedto, Fosamax® (i.e. Alendronate sodium), is used for the prevention ofotosclerosis in the middle ear. If this drug were to be administeredorally, a typical daily oral dose of approximately 10 mg would berequired, with a percentage uptake of the drug from the gut in a fastedstate of approximately 0.6%. This would result in an actual daily doseof approximately 60 mcg/day, and give a theoretical maximum serumconcentration of approximately 12 mcg/liter or 12 ng/ml, assuming 5liters blood volume. In contrast, an effective dose may be delivereddirectly to the middle ear through use of a drug-eluting stapesprosthesis, as described herein. For example, if approximately 1 cc oftissue volume is to be treated in a site-specific way, wherein the drugis delivered directly at the site of action, approximately 12 ng of drugper day is required. Using materials such as, but not limited to,poly(ethylene-co-vinyl acetate) (EVAc) as a matrix to form the piston,with only a 10% drug loading (which is considered to be a very low totalpercentage loading for matrices of such materials), a piston of 2 mmlength and 0.6 mm diameter would contain 52.3 mcg of drug. Thus, at arequirement of 12 ng/day, the piston may be loaded with sufficient drugfor 12 years of therapy (assuming the drug is substantially 100% stablewithin the implant, and the release rate is substantially constant overthe full device lifetime).

Even assuming a less than perfect drug stability and/or linear release,the required drug therapy may be provided for many months or years usingembodiments of the present invention. As such, the limited size of theexemplary devices described herein does not limit drug payload tounacceptably low levels. Rather, reasonable drug delivery rates may beprovided for long periods without the need to increase the size of theprosthesis or to provide additional drug delivery systems or drugstorage receptacles.

In addition to bisphosphonate delivery for the treatment and/orprevention of otosclerosis, embodiments of the invention may be used forthe delivery of other drugs, and for the treatment of other conditionsrelated to the middle and/or inner ear. In one embodiment, thedrug-eluting prosthesis is used for the delivery of antioxidants. Theseantioxidants may, for example, be used for the protection fromototoxicity associated with the use of platinum-based chemotherapeuticagents such as cisplatin. In another embodiment, the drug-elutingprosthesis is used for the delivery of steroids, such as, but notlimited to, Dexamethasone. These steroids may, for example, be used inthe treatment of problems within the ear including, but not limited to,sensorineural hearing loss and Meniere's disease. In another embodiment,the drug-eluting prosthesis is used for the delivery of antibiotics,such as, but not limited to, Gentamicin. These antibiotics may, forexample, be used in the treatment of problems within the ear including,but not limited to, Meniere's disease. In yet another embodiment, thedrug-eluting prosthesis is used for the delivery of anti-apoptoticagents, such as, but not limited to, Caspase inhibitors. Theseanti-apoptotic agents may, for example, be used in the treatment ofproblems within the ear including, but not limited to, noise-inducedhearing loss (NIHL).

Other implantable devices may also be adapted to include a drug-elutingcomponent, allowing for targeted drug delivery to any part of the body.Devices that may utilize this drug-eluting capability include, but arenot limited to, spinal implants or other bone stabilizing implants,pacemakers, insulin delivery devices or other active treatment devices,or any other appropriate device or element that is implanted into abody. The drug-eluting component of these devices may be used to delivera drug, or multiple drugs, including, but not limited to, a painkillingor anesthetic drug, a bone growth enhancing or inhibiting drug, or otherappropriate drugs for the targeted treatment of a specific portion of abody.

Having described certain embodiments of the invention, it will beapparent to those of ordinary skill in the art that other embodimentsincorporating the concepts disclosed herein may be used withoutdeparting from the spirit and scope of the invention. Accordingly, thedescribed embodiments are to be considered in all respects as onlyillustrative and not restrictive.

1. A medical implant device, comprising: a prosthesis adapted to replaceat least a portion of a bone, wherein the prosthesis comprises adrug-eluting polymer adapted to deliver a drug to at least a portion ofan area surrounding the prosthesis.
 2. The medical implant device ofclaim 1, wherein the prosthesis is a stapes prosthesis.
 3. The medicalimplant device of claim 2, wherein the stapes prosthesis comprises awire portion and a piston portion.
 4. The medical implant device ofclaim 3, wherein the drug-eluting polymer surrounds at least one sectionof the wire portion.
 5. The medical implant device of claim 3, whereinthe piston portion comprises the drug-eluting polymer.
 6. The medicalimplant device of claim 5, wherein the piston portion comprises amonolithic polymer matrix having drug molecules distributedtherethrough.
 7. The medical implant device of claim 5, wherein thepiston portion comprises a solid exterior.
 8. The medical implant deviceof claim 7, wherein the piston portion comprises a core, within thesolid exterior, that comprises the drug-eluting polymer.
 9. The medicalimplant device of claim 3, wherein the piston portion comprises asemi-permeable membrane.
 10. The medical implant device of claim 3,wherein the piston portion comprises an impermeable sheath.
 11. A methodof treating a portion of a body, the method comprising: removing adamaged portion of a body; and inserting a prosthesis to replace thedamaged portion of the body, wherein the prosthesis comprises adrug-eluting polymer adapted to deliver at least one drug to at least aportion of an area surrounding the prosthesis.
 12. The method of claim11, wherein the portion of the body comprises a stapes bone.
 13. Themethod of claim 12, wherein the prosthesis is a stapes prosthesis. 14.The method of claim 13, wherein the stapes prosthesis comprises a wireportion and a piston portion.
 15. The method of claim 14, wherein thedrug-eluting polymer surrounds at least one section of the wire portion.16. The method of claim 14, wherein the piston portion comprises thedrug-eluting polymer.
 17. The method of claim 16, wherein the pistonportion comprises a monolithic polymer matrix having drug moleculesdistributed therethrough.
 18. The method of claim 16, wherein the pistonportion comprises a solid exterior.
 19. The method of claim 18, whereinthe piston portion comprises a core, within the solid exterior, thatcomprises the drug-eluting polymer.
 20. The method of claim 14, whereinthe piston portion comprises a semi-permeable membrane.
 21. The methodof claim 14, wherein the piston portion comprises an impermeable sheath.22. A method for manufacturing a medical implant device, the methodcomprising: coupling a wire portion to a piston portion to form aprosthesis, at least one of the wire portion and the piston portioncomprising a drug-eluting polymer adapted to deliver a drug to at leasta portion of an area surrounding the prosthesis.